The objective of this project is to develop successful clinical strategies for the early detection of esophageal cancer. Background: Esophageal cancer is a common malignancy with very poor prognosis, primarily because most tumors produce symptoms only after they have spread beyond the esophageal wall and are unresectable. Significant improvement in survival will require successful strategies to diagnose and treat more cases at earlier, more curable stages of the disease. Methods: The project includes four studies, the Cytology Sampling Study (MSS), the Mucosal Staining Study (MSS), the Endoscopic Ultrasonography Study (EUS), and the Endoscopic Therapy Pilot Study (ETPS), each designed to evaluate a technique that may be useful in a practical early detection program. The project is being carried out in Linxian, China, a county with very high rates of esophageal cancer. Progress: In the CSS study, 439 asymptomatic adults were examined with both balloon and sponge samplers, followed by endoscopy. The sensitivity of the balloon for detecting biopsy-proven squamous dysplasia or cancer was 47%, while the sensitivity of the sponge was only 24% for identifying these lesions. Improved samplers will be needed to increase these baseline figures. In the MSS study, 225 adults were endoscoped. All visible lesions and a control site were described and photographed before and after mucosal iodine staining and then biopsied. Analysis showed that biopsying lesions that were visible before staining identified 63% of the high-grade squamous dysplasia and cancer, but biopsying unstained areas after staining detected 96% of these lesions. Such accurate visualization of high-grade dysplasia and cancer may allow primary endoscopic screening of high-risk individuals in some settings. In the EUS Study, 10 patients had both EUS and esophagectomy. EUS accurately estimated the depth of tumor invasion in 2 of these cases, but overcalled the depth of invasion in the other 8. Higher frequency EUS instruments may be required for accurate staging of these early lesions. In the ETPS, all followup endoscopies of the treated patients showed healing of the treatment sites.